Herpes zoster (or simply zoster), commonly known as shingles and also known as zona, is a viral disease characterized by painful skin lesions (typically, a blistering rash) in a limited area on one side of the body. Shingles is caused by the varicella zoster virus (VZV).
Initial infection with VZV causes the short-lived illness chickenpox, and generally occurs in children. Once an episode of chickenpox has resolved, the virus is not eliminated from the body. Varicella zoster virus becomes latent in the nerve cell bodies and, less frequently, in non-neuronal satellite cells of dorsal root, cranial nerve or autonomic ganglion, without causing any symptoms. Years or decades after a chickenpox infection, the virus may reactivate as shingles. The virus breaks out of nerve cell bodies and travels down nerve axons to cause viral infection of the skin in the region of the nerve (i.e., the dermatome) causing painful skin lesions. Exactly how the virus remains latent in the body, and subsequently reactivates is not understood.
Throughout the world, the annual incidence rate of shingles ranges from 1.2 to 3.4 cases per 1,000 healthy individuals, increasing to 3.9-11.8 per 1,000 individuals older than age 65. Shingles develops in an estimated 500,000 Americans each year.
The earliest symptoms of shingles typically include headache, fever and malaise. These symptoms are commonly followed by sensations of burning pain, itching, hyperesthesia (i.e., oversensitivity), or paresthesia (i.e., tingling, pricking, numbness). Sensations are also described as stinging, aching and/or throbbing, and intermittent quick stabs of agonizing pain.
In most cases, after 1-2 days (but sometimes as long as 3 weeks), the initial phase is followed by the appearance of the characteristic painful skin lesions. The lesions most commonly occur on the torso, but can also appear on the face, eyes or other parts of the body. Shingles causes skin changes limited to a dermatome, normally resulting in a stripe or belt-like pattern that is limited to one side of the body and does not cross the midline.
Later, the lesions become vesicular, forming small blisters filled with a serous exudate, as the fever and general malaise continue. These lesions are typically described as being intensely painful. Since nerves carry the virus and the virus causes inflammation, shingles has been described as having a raw wound inside one's nervous system. Typically, affected individuals cannot even bear clothes touching the lesions. Even a light touch can produce a jolting reaction. Usually, the pain is greater in older patients.
The painful vesicles eventually become cloudy or darkened as they fill with blood, crust over within seven to ten days, and usually the crusts fall off and the skin heals. Sometimes, after severe blistering, scars and discolored skin remain.
Herpes zoster may have additional symptoms, depending on the dermatome involved. Herpes zoster ophthalmicus involves the orbit of the eye and occurs in approximately 10-25% of cases. Symptoms may include conjunctivitis, keratitis, uveitis, and optic nerve palsies that can sometimes cause chronic ocular inflammation, loss of vision, and debilitating pain. Herpes zoster oticus (i.e., Ramsay Hunt syndrome type II) involves the ear. Symptoms include hearing loss and vertigo.
The lesions and pain of shingles usually subside within three to five weeks, but about one in five patients (about one in two patients over age 70) suffer residual nerve pain for months or years, a condition called postherpetic neuralgia. This intensely painful condition is often difficult to manage. The pain may be a constant deep aching or burning. Brief bouts of burning sharp pain may also occur.
In some patients, shingles can reactivate presenting as zoster sine herpete. Pain radiates along the path of a single spinal nerve, but without an accompanying lesion. This condition may involve complications that affect several levels of the nervous system and cause multiple cranial neuropathies, polyneuritis, myelitis, or aseptic meningitis.
Shingles is more likely to occur in people whose immune system is impaired due to aging, immunosuppressive therapy, psychological stress, or other factors. A 2008 study revealed that people with close relatives who have had shingles are twice as likely to develop it themselves, thereby evidencing that genetic factors are involved in those who are more susceptible to VZV.
Current Prevention/Treatment
A live vaccine for VZV exists, marketed as Zostavax®. In a 2005 study of 38,000 older adults, it prevented half the cases of shingles and reduced the number of cases of postherpetic neuralgia by two-thirds. In October 2007, the vaccine was officially recommended in the U.S. for healthy adults aged 60 and over. However, it appears that as people age, the effectiveness of the vaccine diminishes. Additionally, since viruses mutate, the vaccine may lose its efficacy. Also, the vaccine is virtually useless after the onset of shingles. Moreover, numerous adverse reactions have reportedly been linked to the vaccine, ranging from causing a bout of shingles to allergic reactions and even death.
Once shingles is acquired, the aims of treatment are to shorten the duration of an episode, to limit the severity and duration of pain, and reduce complications. Symptomatic treatment is often needed for postherpetic neuralgia. Administration of the GABA analogue, gabapentin, has been found to offer some relief.
Antiviral drugs (e.g., acyclovir, valacyclovir, famciclovir) inhibit VZV replication and reduce the severity and duration of shingles. Antiviral treatment is recommended for all immunocompetent individuals over age 50 during the acute phase of shingles. However, it is critical that antiviral treatment is started within the therapeutic responsive window, i.e., within 72 hours of the first appearance of a characteristic lesion. After 72 hours, the efficacy of the antiviral treatment is greatly diminished.
In people who are at a high risk for repeated attacks of shingles (e.g., AIDS patients), antiviral drugs may be given prophylactically. However, since antiviral drugs may suppress the immune system, they may exacerbate pathological conditions of immunocompromised individuals. Additionally, antivirals are subject to drug resistance, as the pathogens mutate over time, becoming less susceptible to the treatment.
Typically, five daily oral doses of acyclovir are prescribed prophylactically. Common adverse drug reactions associated with systemic acyclovir therapy (oral or IV) include: nausea, vomiting, diarrhea and/or headache. Additional common adverse effects of IV acyclovir include encephalopathy, renal impairment, and injection site reactions.
The pain associated with shingles is treated with systemic analgesics. Occasionally, severe pain may require an opioid medication, such as morphine. Once the lesions have crusted over, capsaicin cream (Zostrix®) can be used. Topical lidocaine and nerve blocks may also reduce pain.
Accordingly, a need exists for an effective and safe method of preventing or inhibiting the pain associated with shingles and postherpetic neuralgia.